BIOCHEMICAL GENETICS
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2022
·Vol. 61
·期 3
·916-930
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IF 2.22
Wang Pengwei,Mao Senlin,Yi Tingting,Wang Lihua
Vascular dementia (VaD) is the second most common subtype of dementia, but the precise mechanism underlying VaD is not fully understood. Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) can act as a key regulator in physiological and pathological processes, including neurological disorders, but whether it is correlated with VaD has not been elucidated. In this study, we established a mouse model of VaD by the transient bilateral common carotid artery occlusion surgery. As expected, the Morris water maze showed that VaD mice had significant deficits in spatial learning and memory. MALAT1 was elevated in the hippocampus of VaD mice. Additionally, we found that microRNA (miR)-9-3p was downregulated in the VaD hippocampus. By performing a dual-luciferase report assay, we verified the binding relationship between MALAT1 and miR-9-3p. Interestingly, synapse-associated protein-97 (SAP97), a well-known gene related to synaptic functions, was found upregulated in the hippocampus of VaD mice. In vitro experiments performed on hippocampal neurons demonstrated that miR-9-3p negatively regulated SAP97 expression. The downregulation of MALAT1 in hippocampal neurons increased miR-9-3p and reduced SAP97, whereas miR-9-3p inhibition rescued the MALAT1 downregulation-mediated SAP97 reduction. In conclusion, the present study reported the alterations in the expression levels of MALAT1, miR-9-3p, and SAP97 in the hippocampus of VaD mice, suggesting that MALAT1 targets miR-9-3p to upregulate SAP97 in the hippocampus of mice with VaD. This work will be helpful for understanding the molecular mechanisms of VaD.
研究领域:
神经科学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
Metabolites
·
2022
·Vol. 12
·期 9
·841
·
IF 5.581
Simeng Zhang,Yuchan Deng,Annan Zhang,Lili Yan,Zhichao Zhang,Jing Wei,Qiang Zhang
The transitional expression and aggregation of amyloid β (Aβ) are the most important causative factors leading to the deterioration of Alzheimer’s disease (AD), a commonly occurring metabolic disease among older people. Antioxidant agents such as vitamin C (Vc) have shown potential effects against AD and aging. We applied an liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method and differential metabolites strategy to explore the metabolic disorders and Vc restoration in a human Aβ transgenic (Punc-54::Aβ1–42) nematode model CL2006. We combined the LC-MS/MS investigation with the KEGG and HMDB databases and the CFM-ID machine-learning model to identify and qualify the metabolites with important physiological roles. The differential metabolites responding to Aβ activation and Vc treatment were filtered out and submitted to enrichment analysis. The enrichment showed that Aβ mainly caused abnormal biosynthesis and metabolism pathways of phenylalanine, tyrosine and tryptophan biosynthesis, as well as arginine and proline metabolism. Vc reversed the abnormally changed metabolites tryptophan, anthranilate, indole and indole-3-acetaldehyde. Vc restoration affected the tryptophan metabolism and the biosynthesis of phenylalanine, tyrosine and tryptophan. Our findings provide supporting evidence for understanding the metabolic abnormalities in neurodegenerative diseases and the repairing effect of drug interventions.Keywords:Alzheimer’s disease;dementia;neurodegenerative disease;aging;Aβ;metabolism;amino acid;ascorbic acid
研究领域:
神经科学
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代谢组学
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药理学
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生物化学
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DOI
PubMed
高影响因子
Frontiers in Public Health
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2025
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IF 3.4
Patricia Ferrero-Sereno,María Mendoza-Muñoz,Patricia Palomo-López,Jorge Carlos-Vivas,Patricia Luna-Castaño,Raquel Caballero-De la Calle,Miguel Ángel García-Garrido,Laura Muñoz-Bermejo
Background: Informal caregivers of people with dementia present high levels of burden, emotional distress and low social support. Technology-based home-based interventions are presented as an alternative to providing health education, emotional support and caregiver training.Objective: To evaluate the effectiveness of technological interventions on health-related quality of life (HRQoL) and the management of psychoemotional aspects in family caregivers of people with dementia.Methods: A systematic literature review (SLR) was conducted using the Web of Science, PubMed and Scopus electronic databases, including all studies up to 7 February 2025.Results: In the review, 7,230 studies were initially identified, but only 13 met the eligibility criteria. The interventions reviewed differed in methodology when examining their impact on target variables. However, on-demand, internet- or telephone-based interventions with training activities and contact with professionals seem to improve quality of life and psychoemotional variables such as anxiety, depression and overload.Conclusion: Technological interventions using the internet and mobile applications may be useful for informal caregivers of people with dementia as they can improve quality of life and psychoemotional aspects. The interventions reviewed differed in terms of instruments and protocols when examining their impact on caregiver well-being. Therefore, more research is needed to further investigate these methodologies in order to optimize their impact and adapt them to the diverse realities of caregivers of people with dementia.
研究领域:
老年医学
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护理学
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临床心理学
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康复医学
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数字健康
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公共卫生
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
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IF 6.7
Yong-xin Chen,Hong Yang,Da-song Wang,Ting-ting Chen,Xiao-lan Qi,Ling Tao,Yan Chen,Xiang-chun Shen
Background Mitochondrial dysfunction is key to the pathogenesis of vascular dementia (VaD). Sirtuin-3 (SIRT3), an essential member of the sirtuins family, has been proven to be a critical sirtuin in regulating mitochondrial function. The phenolic glucoside gastrodin (GAS), a bioactive ingredient from Gastrodiae Rhizome (known in Chinese as Tian ma) demonstrates significant neuroprotective properties against central nervous system disorders; however, the precise mechanisms through which GAS modulates VaD remain elusive. Purpose This study aims to investigate whether GAS confers a protective role against VaD, and to figure out the underlying molecular mechanisms. Methods A bilateral common carotid artery occlusion (BCCAO)-mediated chronic cerebral hypoperfusion (CCH) VaD rat model and a hypoxia model using HT22 cells were employed to investigate pharmacological properties of GAS in mitigating mitochondrial dysfunction. A SIRT3 agonist resveratrol (RES), a SIRT3 inhibitor 3-TYP and SIRT3-knockdown in vitro were used to explore the mechanism of GAS in association with SIRT3. The ability of SIRT3 to bind and deacetylate TFAM was detected by immunoprecipitation assay, and TFAM acetylation sites were further validated using mass spectrometry. Results GAS increased SIRT3 expression and ameliorated mitochondrial structure, mitochondrial respiration, mitochondrial dynamics along with upregulated mitochondrial transcription factor A (TFAM), mitigating oxidative stress and senescence. Comparable results were noted with the SIRT3 agonist RES, indicating an impactful neuroprotection played by SIRT3. Specifically, the attenuation of SIRT3 expression through knockdown techniques or exposure to the SIRT3 inhibitor 3-TYP in HT22 cells markedly abrogated GAS-mediated mitochondrial rescuing function. Furthermore, our findings elucidate a novel facet: SIRT3 interacted with and deacetylated TFAM at the K5, K7, and K8 sites. Decreased SIRT3 is accompanied by hyper-acetylated TFAM. Conclusion The present results were the first to demonstrate that the SIRT3/TFAM pathway is a protective target for reversing mitochondrial dysfunction in VaD. The findings suggest that GAS-mediated modulation of the SIRT3/TFAM pathway, a novel mechanism, could ameliorate CCH-induced VaD, offering a potentially beneficial therapeutic strategy for VaD.
研究领域:
神经科学
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药理学
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分子生物学
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病理生理学
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DOI
PubMed
高影响因子
CELL DEATH AND DIFFERENTIATION
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2024
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IF 13.7
Wu Yachen,Zheng Wenzhong,Xu Guofeng,Zhu Lijun,Li Zhiqiang,Chen Jincao,Wang Lianrong,Chen Shi
Sterol regulatory element binding transcription factors (SREBPs) play a crucial role in lipid homeostasis. They are processed and transported to the nucleus via COPII, where they induce the expression of lipogenic genes. COPII maintains the homeostasis of organelles and plays an essential role in the protein secretion pathways in eukaryotes. The formation of COPII begins at endoplasmic reticulum exit sites (ERES), and is regulated by SEC16A, which provides a platform for the assembly of COPII. However, there have been few studies on the changes in SEC16A protein levels. The repetitive expansion of the hexanucleotide sequence GGGGCC within the chromosome 9 open reading frame 72 (C9orf72) gene is a prevalent factor in the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we found that the absence of C9orf72 leads to a decrease in SEC16A protein levels, resulting in reduced localization of the guanine nucleotide exchange factor SEC12 at the ERES. Consequently, the small GTP binding protein SAR1 is unable to bind the endoplasmic reticulum normally, impairing the assembly of COPII. Ultimately, the disruption of SREBPs transport decreases de novo lipogenesis. These results suggest that C9orf72 acts as a novel role in regulating lipid homeostasis and may serve as a potential therapeutic target for obesity.
研究领域:
分子生物学
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脂质代谢
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神经退行性疾病
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2023
·
IF 5
Mo-li Zhu,Jie Zhang,Li-juan Guo,Rui-zhu Yue,Shan-shan Li,Bao-yue Cui,Shuang Guo,Qian-qian Niu,Ya-nan Yu,Huan-huan Wang,Lin Yang,Ya-ling Yin,Shuang-xi Wang,He-qin Zhan,Zhi-tao Gao,Peng Li
Vascular dementia (VD) is one of the most common causes of dementia, taking account for about 20% of all cases. Although studies have found that selenium supplementation can improve the cognitive ability of Alzheimer's patients, there is currently no research on the cognitive impairment caused by VD. This study aimed to investigate the role and mechanism of Amorphous selenium nanodots (A SeNDs) in the prevention of VD. The bilateral common carotid artery occlusion (BCCAO) method was used to establish a VD model. The neuroprotective effect of A SeNDs was evaluated by Morris water maze , Transcranial Doppler TCD, hematoxylin–eosin (HE) staining , Neuron-specific nuclear protein (Neu N) staining and Golgi staining. Detect the expression levels of oxidative stress and Calcium-calmodulin dependent protein kinase II (CaMK II), N-methyl-D-aspartate receptor subunit NR2A, and postsynaptic dense protein 95 (PSD95). Finally, measure the concentration of calcium ions in neuronal cells. The results showed that A SeNDs could significantly improve the learning and memory ability of VD rats, restore the posterior arterial blood flow of the brain, improve the neuronal morphology and dendritic remodeling of pyramidal cells in hippocampal CA1 area, reduce the level of oxidative stress in VD rats, increase the expression of NR2A, PSD95, CaMK II proteins and reduce intracellular calcium ion concentration, but the addition of selective NR2A antagonist NVP-AAMO77 eliminated these benefits. It suggests that A SeNDs may improve cognitive dysfunction in vascular dementia rats by regulating the NMDAR pathway.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Qian Yu,Xian Qiu,Jing Zhong,Chao Cao,Yuechan Liao,Zhiwei Zeng,Dawei Zhang,Chunyan Yan
Acorus tatarinowii , a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF- α , IL-1 β , PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50–3 was obtained from AT50. Structural analysis indicated ATP50–3 consisted of α -L-Ara f -(1→, →2)- α -L-Ara f -(1→, →3)- α -L-Ara f -(1→, →5)- α -L-Ara f -(1→, α -D-Xyl p -(1→, →3,4)- β -D-Xyl p -(1→, →3)- α -D-Gal p -(1→, →3,6)- α -D-Gal p -(1→, →6)-4-OAc- α -D-Gal p -(1→, →3,4,6)- α -D-Gal p -(1→, →4)- α -D-Glc p -(1→, →2,3,6)- β -D-Glc p -(1→, →4,6)- α -D-Man p -(1→, →3,4)- α -L-Rha p -(1→, →4)- α -D-Gal p A-(1→, and →4)- α -D-Glc p A-(1 → residues and terminated with Xyl and Ara. Additionally, ATP50–3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50–3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.
研究领域:
药理学
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神经科学
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传统中药
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
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IF 2.3
Xue-Song Tang,Lin-Yu He,Sheng-Nan Li,Wen-Cheng Zhang,Ze-Yu Wu,Ai-Ling Hui
Vascular dementia (VaD) is a neurodegenerative disease resulting from cerebral vascular obstruction, leading to cognitive impairment, and currently lacks effective treatment options. Due to its complex pathogenesis, multi-target drug design (MTDLs) strategies are considered among the most promising therapeutic approaches. In this study, we designed and synthesized a series of novel indanone derivatives targeting targets related to vascular health and dementia. The results indicated that compound C 5 exhibited excellent acetylcholinesterase inhibitory activity (IC 50 =1.16 0.41 μM) and anti-platelet aggregation activity (IC 50 =4.92±0.10 μM) within ranges of 0.1–1000 μM and 0.03–300 μM, respectively, possibly mediated by molecular docking interactions. Furthermore, compound C 5 demonstrated protective effects on cells at concentrations ≤50 μM, significantly reducing the release of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) in a concentration-dependent manner, showcasing its potent neuroinflammatory inhibitory effects. Anti-inflammatory therapies are regarded as effective strategies for treating VaD. Therefore, compound C 5 holds promise as a novel candidate drug for further investigation into the treatment of vascular dementia. Graphical
研究领域:
神经病学
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药理学
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药物设计
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
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IF 5.2
Ting Li,Wenzhu Wang,Weijin Liu,Mingming Sun,Qiuying Wang,Zihan Li,Jie Hao,Yan Yu
Vascular dementia (VD) is the second leading cause of cognitive impairment after Alzheimer’s disease, posing a heavy burden to families and society. The majority of causes of VD are vascular diseases such as stroke, with ischemic stroke accounting for a large proportion. After ischemia–reperfusion, factors such as mitochondrial damage and increased xanthine oxidase lead to excessive production of reactive oxygen species (ROS) at the ischemic site, further exacerbating brain injury. Therefore, developing effective ROS scavengers is crucial. Polydopamine has become one of the widely used surface functionalized materials in recent years, due to its excellent biocompatibility and antioxidant properties. This paper proposed a macrophage membrane disguised polydopamine (PDA) nanoplatform for loading the neuroprotective drug puerarin (PUE). The as made PUE@PDA@CMs (PPCs) nanoplatforms can significantly and effectively clear ROS, alleviate oxidative microenvironment, and protect neurons from oxidative stress damage. The macrophage membranes modification enables PPCs to respond to lymphocyte recruitment at the site of cerebral ischemia–reperfusion injury, thereby targeting and aggregating to the injury site. In a mouse model of vascular dementia, PPCs treatment significantly reduced neuronal apoptosis and provided significant cognitive and memory function recovery, providing new strategies and prospects for the treatment of central nervous system diseases.
研究领域:
神经科学
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药剂学
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材料科学
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痴呆研究
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产品关联
DOI
PubMed
高影响因子
Cell Communication and Signaling
·
2020
·Vol. 18
·期 1
·1-16
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IF 4.344
Yan Mei-Ling,Zhang Shuai,Zhao Hong-Mei,Xia Sheng-Nan,Jin Zhuo,Xu Yi,Yang Lin,Qu Yang,Huang Si-Yu,Duan Ming-Jing,Mao Meng,An Xiao-Bin,Mishra Chandan,Zhang Xin-Yu,Sun Li-Hua,Ai Jing
Background Chronic brain hypoperfusion (CBH) is closely related to Alzheimer’s disease (AD) and vascular dementia (VaD). Meanwhile, synaptic pathology plays a prominent role in the initial stage of AD and VaD. However, whether and how CBH impairs presynaptic plasticity is currently unclear.Methods In the present study, we performed a battery of techniques, including primary neuronal culture, patch clamp, stereotaxic injection of the lentiviral vectors, morris water maze (MWM), dual luciferase reporter assay, FM1–43 fluorescence dye evaluation, qRT-PCR and western blot, to investigate the regulatory effect of miR-153 on hippocampal synaptic vesicle release both in vivo and in vitro. The CBH rat model was generated by bilateral common carotid artery ligation (2VO).Results Compared to sham rats, 2VO rats presented decreased field excitatory postsynaptic potential (fEPSP) amplitude and increased paired-pulse ratios (PPRs) in the CA3-CA1 pathway, as well as significantly decreased expression of multiple vesicle fusion-related proteins, including SNAP-25, VAMP-2, syntaxin-1A and synaptotagmin-1, in the hippocampi. The levels of microRNA-153 (miR-153) were upregulated in the hippocampi of rats following 2VO surgery, and in the plasma of dementia patients. The expression of the vesicle fusion-related proteins affected by 2VO was inhibited by miR-153, elevated by miR-153 inhibition, and unchanged by binding-site mutation or miR masks. FM1–43 fluorescence images showed that miR-153 blunted vesicle exocytosis, but this effect was prevented by either 2′-O-methyl antisense oligoribonucleotides to miR-153 (AMO-153) and miR-masking of the miR-153 binding site in the 3′ untranslated region (3’UTR) of the Snap25, Vamp2, Stx1a and Syt1 genes. Overexpression of miR-153 by lentiviral vector-mediated miR-153 mimics (lenti-pre-miR-153) decreased the fEPSP amplitude and elevated the PPR in the rat hippocampus, whereas overexpression of the antisense molecule (lenti-AMO-153) reversed these changes triggered by 2VO. Furthermore, lenti-AMO-153 attenuated the cognitive decline of 2VO rats.Conclusion sOverexpression of miR-153 controls CBH-induced presynaptic vesicle release impairment by posttranscriptionally regulating the expression of four vesicle release-related proteins by targeting the 3’UTRs of the Stx1a, Snap25, Vamp2 and Syt1 genes. These findings identify a novel mechanism of presynaptic plasticity impairment during CBH, which may be a new drug target for prevention or treatment of AD and VaD.
Video Abstract
Graphical abstract
研究领域:
神经科学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2020
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IF 5.977
Gui-Sheng Zhou,Yi-Chu Yuan,You Yin,Yu-Ping Tang,Ren-Jie Xu,Yan Liu,Pei-Dong Chen,Lian Yin,Jin-Ao Duan
A sensitive, rapid, precise and specific analytical method of hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (HILIC-UHPLC–QTRAP®/MS 2 ) combined with a high-efficiency and easy sample preparation technology of ultrasound-assisted ionic liquid dispersive liquid–liquid microextraction (UA-IL-DLLME) was developed to investigate neurotransmitters (NTs) in mild cognitive impairment, mild dementia and moderate dementia patients’ urine samples. Firstly, the UA-IL-DLLME parameters were optimized using Plackett–Burman screening and rotatable central composite design, and the main optimal conditions were obtained: ultrasound power of 307 W, ultrasound time of 4.3 min and agitation time of 4.8 min. Secondly, HILIC-UHPLC–QTRAP®/MS 2 method was developed to simultaneously determine 15 underivatized NTs in urine samples. The analysis results of clinical samples showed that some NTs such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamic acid (Glu) presented significant differences in different dementia stages. Finally, multivariate analysis based on the combination of principal component analysis and supervised counter propagation artificial neural network was developed for comprehensive analysis of the obtained clinical data sets. As a result, GABA and Glu were simultaneously presented meaningful contribution for classification of samples, and might be considered as potential differential compounds to the urine samples from cluster patients with different dementia stages. In summary, the presented strategy of preparation, analysis and statistics might be used to investigate NTs in different clinical biological fluids.
研究领域:
分析化学
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医学
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神经科学
✓ 已验证
DOI
高影响因子
Frontiers in Behavioral Neuroscience
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2021
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IF 3.558
Zhu Tiantian,Zhu Moli,Qiu Yue,Wu Zeqing,Huang Ning,Wan Guangrui,Xu Jian,Song Ping,Wang Shuangxi,Yin Yaling,Li Peng
Cerebral ischemia triggers vascular dementia (VD), which is characterized by memory loss, cognitive deficits, and vascular injury in the brain. Puerarin (Pur) represents the major isoflavone glycoside of Radix Puerariae, with verified neuroprotective activity and cardiovascular protective effects. However, whether Pur ameliorates cognitive impairment and vascular injury in rats with permanent occlusion of bilateral common carotid arteries (BCCAO) remains unknown. This work aimed to assess Pur’s effects on BCCAO-induced VD and to dissect the underlying mechanisms, especially examining the function of transient receptor potential melastatin-related 2 (TRPM2) in alleviating cognitive deficits and vascular injuries. Rats with BCCAO developed VD. Pur (50, 100, and 150 mg/kg) dose-dependently attenuated the pathological changes, increased synaptic structural plasticity in the dorsal CA1 hippocampal region and decreased oxidative stress, which eventually reduced cognitive impairment and vascular injury in BCCAO rats. Notably, Pur-improved neuronal cell loss, synaptic structural plasticity, and endothelial vasorelaxation function might be mediated by the reactive oxygen species (ROS)-dependent TRPM2/NMDAR pathway, evidenced by decreased levels of ROS, malondialdehyde (MDA), Bax, Bax/Bcl2, and TRPM2, and increased levels of superoxide dismutase (SOD), Bcl2, and NR2A. In conclusion, Pur has therapeutic potential for VD, alleviating neuronal cell apoptosis and vascular injury, which may be related to the ROS-dependent TRPM2/NMDAR pathway.
研究领域:
神经科学
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药理学
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心血管研究
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产品关联
DOI
PubMed
高影响因子
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